Could rTMS Be A Novel Treatment For Anorexia Nervosa?
A new meta-analysis says...yes!
One of the very exciting things about working on the sharpest part of the bleeding edge of neuromodulation is how fast and furious new data is coming about, and since these methods are safe, able to change practice rapidly.
Today, thanks to my friend Arjun Nanda, M.D., host of The Mental Health Forecast podcast on which I have appeared, along with
in yet another episode…I learned about the following hopeful review.Efficacy of transcranial magnetic stimulation in anorexia nervosa: a systematic review and meta-analysis
This newsletter is becoming the Meta-analysis Star-Ledger,1 but I’ll take it.
In this paper, the authors evaluate the role of TMS treatment in Anorexia Nervosa. I haven't spent a heck of a lot of time on eating disorders (EDOs) on these digital pages, mostly cause I didn’t have a lot to say that was new or useful. The treatment for restrictive EDOs has traditionally been…food. This is a tough sell for people with such disorders. It’s briefly worth noting that EDOs are the most high lethality conditions in the field of psychiatry. That is right, it’s not depression—not by a long shot. It’s eating disorders that are most likely to lead to death. For example:
The crude mortality rate was 5.1%. The standardized mortality ratios for death (9.6) and suicide (58.1) were significantly elevated (p < .001).2
Somewhat surprisingly, being hospitalized for a mood disorder in women with co-occurring mood disorders is protective…
Standardized mortality ratios were elevated for all causes of mortality (11.6; 95% confidence interval, 5.5-21.3) and suicide(56.9; 95% confidence interval, 15.3-145.7) in anorexia nervosa but not for death (1.3; 95% confidence interval, 0.0-7.2) in bulimia nervosa. Predictors of mortality in anorexia nervosa included severity of alcohol use disorder during follow-up (P<.001). Hospitalization for an affective disorder before baseline assessment seemed to protect women from a fatal outcome (P<.001).3
Now, given the data about how fatal these problems are, let’s move on to the news. With transcranial magnetic stimulation, we might have a new effective treatment toolkit! In what is likely a thankless task, the authors screened 2772 publications for inclusion. They had enough data to include nine papers in the meta-analysis.
A primer on how to interpret Meta-Analysis data is here. And a more extensive dive is available in chapter one of my book, Inessential Pharmacology. (amazon affiliate link).
This is—to be clear—only data on Anorexia Nervosa, not other eating disorders.
Who was in the study:
The present meta-analysis consists of 129 participants with a mean age of 32.41 ± 7.27 years and a mean disease duration of 14.57 ± 6.66 years.
Where did they stimulate in the brain? A range of targets!
The most common location of the TMS coil was the left dlPFC [Left DorsoLateral Prefrontal Cortex…a.k.a. the left front of the brain), in two studies was dorsomedial prefrontal cortex (dmPFC), in one study was inferior parietal lobe, and in one study was the insula.
They force us to do math with that sentence… 9 - 5 = 4 L-dlPFC studies.
The BMI difference (gaining weight in a healthy way) is just barely significant…
BMI of patients significantly increased after TMS (SMD = −0.255, 95% CI: −0.505 to −0.005, and P-value = 0.045)
However, when we look at a standardized eating disorder outcome measure that is a bit more subjective—a rating scale called the EDE-Q, we get a much larger effect size:
EDE-Q global score was significantly diminished (SMD: 0.634, 95% CI; 0.349 to 0.919, and P-value < 0.001)
Adverse effects were limited across studies, but included suicide attempts (in a cohort with a high risk of suicide):
One study found that five patients experienced undernutrition and health deterioration in both sham and active rTMS conditions, with two in the rTMS group attempting suicide [28]. Another study reported significant discomfort for all participants during stimulation, which lessened over time; one patient withdrew due to severe pain from tapping sensations [37].
The largest study was the Dalton paper, called the TIARA trial—a great study name if ever there was one— and it drove much of the results as a larger RCT. However, it seems there are a range of possible targets for Anorexia, and the results are more promising than most other biological interventions. The attempted suicides are not understood to be causal, but every effort should be made to determine if that risk exists with brain stimulation treatment also, much as it does in oral antidepressants.
For scientists, clinicians, and patients struggling with AN, rTMS seems like a promising option. Of course, this means that it will be submitted— and denied—by most payors because there is no FDA label, and even if there were, it would still be considered experimental and unproven, much like parachutes. However, perhaps for my readers working hard every day at payors, at the very least, it might be time to remove Anorexia Nervosa as an exclusionary criterion and allow patients with depression and anorexia to avail themselves of what might be a helpful treatment?
I know, I know, but a guy can hope?
Bahadori, A. R., Javadnia, P., Bordbar, S., Zafari, R., Taherkhani, T., Davari, A., Tafakhori, A., Shafiee, S., & Ranji, S. Efficacy of transcranial magnetic stimulation in anorexia nervosa: A systematic review and meta-analysis. Eating and Weight Disorders, 30(1), 4. https://doi.org/10.1007/s40519-025-01716-5
Herzog, D. B., Greenwood, D. N., Dorer, D. J., Flores, A. T., Ekeblad, E. R., Richards, A., Blais, M. A., & Keller, M. B. (2000). Mortality in eating disorders: A descriptive study. International Journal of Eating Disorders, 28(1), 20-26. https://doi.org/10.1002/(SICI)1098-108X(200007)28:1<20::AID-EAT3>3.0.CO;2-X
Keel, P. K., Dorer, D. J., Eddy, K. T., Franko, D., Charatan, D. L., & Herzog, D. B. (2003). Predictors of mortality in eating disorders. Archives of general psychiatry, 60(2), 179-183.